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1.
PLoS Genet ; 19(1): e1010592, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36608114

RESUMO

Meiotic recombination is a driving force for genome evolution, deeply characterized in a few model species, notably in the budding yeast Saccharomyces cerevisiae. Interestingly, Zip2, Zip3, Zip4, Spo16, Msh4, and Msh5, members of the so-called ZMM pathway that implements the interfering meiotic crossover pathway in S. cerevisiae, have been lost in Lachancea yeast species after the divergence of Lachancea kluyveri from the rest of the clade. In this context, after investigating meiosis in L. kluyveri, we determined the meiotic recombination landscape of Lachancea waltii. Attempts to generate diploid strains with fully hybrid genomes invariably resulted in strains with frequent whole-chromosome aneuploidy and multiple extended regions of loss of heterozygosity (LOH), which mechanistic origin is so far unclear. Despite the lack of multiple ZMM pro-crossover factors in L. waltii, numbers of crossovers and noncrossovers per meiosis were higher than in L. kluyveri but lower than in S. cerevisiae, for comparable genome sizes. Similar to L. kluyveri but opposite to S. cerevisiae, L. waltii exhibits an elevated frequency of zero-crossover bivalents. Lengths of gene conversion tracts for both crossovers and non-crossovers in L. waltii were comparable to those observed in S. cerevisiae and shorter than in L. kluyveri despite the lack of Mlh2, a factor limiting conversion tract size in S. cerevisiae. L. waltii recombination hotspots were not shared with either S. cerevisiae or L. kluyveri, showing that meiotic recombination hotspots can evolve at a rather limited evolutionary scale within budding yeasts. Finally, L. waltii crossover interference was reduced relative to S. cerevisiae, with interference being detected only in the 25 kb distance range. Detection of positive inference only at short distance scales in the absence of multiple ZMM factors required for interference-sensitive crossovers in other systems likely reflects interference between early recombination precursors such as DSBs.


Assuntos
Meiose , Troca Genética , Proteínas de Ligação a DNA/genética , Meiose/genética , Proteínas Associadas aos Microtúbulos/genética , Proteínas MutL/genética , Saccharomycetales/genética , Saccharomycetales/metabolismo , Ubiquitina-Proteína Ligases/genética
2.
Prague Med Rep ; 125(1): 69-78, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38470440

RESUMO

Gorlin-Goltz syndrome (GGS) is an infrequent multisystemic disease with an autosomal dominant trait, which depicted presence of numerous basal cell carcinoma in conjunction with multiorgan abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the keratocystic odontogenic tumour are usually one of the first manifestations of the syndrome. This article includes a case report of the GGS with regard to its history, incidence, etiology, features, investigations, diagnostic criteria, keratocystic odontogenic tumour and treatment modalities.


Assuntos
Síndrome do Nevo Basocelular , Carcinoma Basocelular , Tumores Odontogênicos , Neoplasias Cutâneas , Criança , Humanos , Síndrome do Nevo Basocelular/diagnóstico , Fenótipo
3.
Mol Biol Evol ; 39(11)2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36205042

RESUMO

The appearance of genomic variations such as loss of heterozygosity (LOH) has a significant impact on phenotypic diversity observed in a population. Recent large-scale yeast population genomic surveys have shown a high frequency of these events in natural isolates and more particularly in polyploids. However, the frequency, extent, and spectrum of LOH in polyploid organisms have never been explored and are poorly characterized to date. Here, we accumulated 5,163 LOH events over 1,875 generations in 76 mutation accumulation (MA) lines comprising nine natural heterozygous diploid, triploid, and tetraploid natural S. cerevisiae isolates from different ecological and geographical origins. We found that the rate and spectrum of LOH are variable across ploidy levels. Of the total accumulated LOH events, 8.5%, 21%, and 70.5% of them were found in diploid, triploid, and tetraploid MA lines, respectively. Our results clearly show that the frequency of generated LOH events increases with ploidy level. In fact, the cumulative LOH rates were estimated to be 9.3 × 10-3, 2.2 × 10-2, and 8.4 × 10-2 events per division for diploids, triploids, and tetraploids, respectively. In addition, a clear bias toward the accumulation of interstitial and short LOH tracts is observed in triploids and tetraploids compared with diploids. The variation of the frequency and spectrum of LOH events across ploidy level could be related to the genomic instability, characterizing higher ploidy isolates.


Assuntos
Saccharomyces cerevisiae , Tetraploidia , Saccharomyces cerevisiae/genética , Triploidia , Ploidias , Perda de Heterozigosidade
4.
Inorg Chem ; 62(38): 15777-15789, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37695678

RESUMO

Three 3-pyridyl-containing small organic bisamide molecules attached with innocent L-phenylalanine (PHE) side chain as building blocks and positional isomeric toluoyl terminals (PME, MME, and OME) have rationally been designed and synthesized for developing a new series of ZnII-coordination complexes. One of the unique molecular frameworks, having two hydrogen bond-equipped monodentate metal-coordinating sites and biologically potent chiral PHE moiety, was combined with ZnII halide salts under various conditions to produce the coordination complexes (CC1-CC7), thoroughly characterized by the single-crystal X-ray diffraction (SXRD) technique. Maintaining the similar component ratios of acquired CCs in 1:1 DMSO-water produced low-molecular weight metallogels (LMWGs) of PME/MME as envisaged from a rheology- and crystal engineering-based structural rationale. A structure-property correlation from the basis of PXRD of the bulk and xerogels and SXRD data of the isolated single crystals of reaction products clearly supports the crystal engineering-based design strategy based on which the metallogels are prepared. Hand-ground nanoscale ZnCl2-based coordination complex CC1 of PME was also studied for cytotoxicity (HEK-293 cell line) and anticancer activities (B16-F10 cell line) in the MTT assay.


Assuntos
Complexos de Coordenação , Humanos , Complexos de Coordenação/farmacologia , Células HEK293 , Fenilalanina/farmacologia , Zinco
5.
Org Biomol Chem ; 21(11): 2375-2389, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36852913

RESUMO

A well-known nonsteroidal anti-inflammatory drug (NSAID), flurbiprofen (FLR), was first conjugated individually with two naturally occurring amino acids such as L-phenylalanine (PHE) and L-alanine (ALA). These covalent amidic bioconjugates were further reacted individually with mafenide (a drug for treating burn wounds) and amantadine (an antiviral drug) to develop primary ammonium monocarboxylate (PAM) salts. Interestingly, both the PHE-containing multidrug salts exhibited significant gelation ability with various solvents including biologically potent water or methyl salicylate (MS). The isolated hydrogel (HG) as well as all the organogels obtained from multidrug gelators were extensively characterized by dynamic rheology and rheoreversibility studies. The hydrogel of FLR·PHE·MAF and MS gels of FLR·PHE·AMN/FLR·AMN were also selectively characterized by table-top and FEG-TEM analyses. The temperature-dependent 1H-NMR spectroscopy of the selected HG further provided insights into the gelation mechanism and the only isolated single-crystal of the weakly diffracted gelator FLR·AMN also revealed the presence of 1D hydrogen-bonded networks. The pure hydrogelator FLR·PHE·MAF salt (which is also an ambidextrous gelator) was found to be promising in both mechanical (rheoreversible) and biological applications and was found to be effective in cytotoxicity, biocompatibility, anti-cancer activity (MTT and cell migration assay), antibacterial response (zone inhibition, turbidity, INT, and resazurin assay) and haemolysis studies.


Assuntos
Flurbiprofeno , Hidrogéis , Hidrogéis/farmacologia , Hidrogéis/química , Flurbiprofeno/farmacologia , Mafenida , Fenilalanina/farmacologia , Sais/química
6.
J Intensive Care Med ; 37(6): 803-809, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34459680

RESUMO

BACKGROUND: Neurological prognosis after cardiac arrest remains ill-defined. Plasma brain natriuretic peptide (BNP) may relate to poor neurological prognosis in brain-injury patients, though it has not been well studied in survivors of cardiac arrest. METHODS: We performed a retrospective review and examined the association of BNP with mortality and neurological outcomes at discharge in a cohort of cardiac arrest survivors enrolled from January 2012 to December 2016 at the Wake Forest Baptist Hospital, in North Carolina. Cerebral performance category (CPC) and modified Rankin scales were calculated from the chart based on neurological evaluation performed at the time of discharge. The cohort was subdivided into quartiles based on their BNP levels after which multivariable adjusted logistic regression models were applied to assess for an association between BNP and poor neurological outcomes as defined by a CPC of 3 to 4 and a modified Rankin scale of 4 to 5. RESULTS: Of the 657 patients included in the study, 254 patients survived until discharge. Among these, poor neurological status was observed in 101 (39.8%) patients that had a CPC score of 3 to 4 and 97 patients (38.2%) that had a modified Rankin scale of 4 to 5. Mean BNP levels were higher in patients with poor neurological status compared to those with good neurological status at discharge (P = .03 for CPC 3-4 and P = .02 for modified Rankin score 4-5). BNP levels however, did not vary significantly between patients that survived and those that expired (P = .22). BNP did emerge as a significant discriminator between patients with severe neurological disability at discharge when compared to those without. The area under the curve for BNP predicting a modified Rankin score of 4 to 5 was 0.800 (95% confidence interval [CI] 0.756-0.844, P < .001) and for predicting CPC 3 to 4 was 0.797 (95% CI 0.756-0.838, P < .001). BNP was able to significantly improve the net reclassification index and integrated discriminatory increment (P < .05). BNP was not associated with long-term all-cause mortality (P > .05). CONCLUSIONS: In survivors of either inpatient or out-of-hospital cardiac arrest, increased BNP levels measured at the time of arrest predicted severe neurological disability at discharge. We did not observe an independent association between BNP levels and long-term all-cause mortality. BNP may be a useful biomarker for predicting adverse neurological outcomes in survivors of cardiac arrest.


Assuntos
Peptídeo Natriurético Encefálico , Parada Cardíaca Extra-Hospitalar , Biomarcadores , Humanos , Prognóstico , Estudos Retrospectivos , Sobreviventes
7.
J Intensive Care Med ; 36(5): 550-556, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32242492

RESUMO

BACKGROUND: Acute kidney injury (AKI) is common among cardiac arrest survivors. However, the outcomes and predictors are not well studied. METHODS: This is a cohort study of cardiac arrest patients enrolled from January 2012 to December 2016 who were able to survive for 24 hours post-cardiopulmonary resuscitation. Patients with anuria, chronic kidney disease (stage 5), and end-stage renal disease were excluded. Acute kidney injury (stage 1) or higher was defined using Kidney Disease: Improving Global Outcomes classification. Multivariable adjusted regression models were used to compute hazard ratio (HR) for association of AKI with risk of mortality and odds ratio (OR) with risk of poor neurological outcomes after adjusting for demographics, comorbidities, and medical therapy. Multivariable logistic regression model was used to compute OR for association of various predictors with AKI. RESULTS: Of 842 cardiac arrest survivors, 588 (69.8%) developed AKI. Among AKI patients, 69.4% died compared with 52.0% among non-AKI patients. In multivariable adjusted Cox proportional hazard model, development of AKI post-cardiac arrest was significantly associated with mortality (HR: 1.35; 95% confidence interval [CI]: 1.07-1.71, P = .01) and poor neurological outcomes defined as cerebral performance category >2 (OR: 2.27; 95% CI: 1.45-3.57, P < .001) and modified Rankin scale >3 (OR: 2.22; 95% CI: 1.43-3.45, P < .001). Postdischarge dialysis was also associated with increased risk of mortality (HR: 2.57; 95% CI: 1.57-4.23, P < .001). Use of vasopressors was strongly associated with development of AKI and continued need for postdischarge dialysis. CONCLUSIONS: Acute kidney injury was associated with increased risk of mortality and poor neurological outcomes. There is need for further studies to prevent AKI in cardiac arrest survivors.


Assuntos
Injúria Renal Aguda , Parada Cardíaca , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Assistência ao Convalescente , Estudos de Coortes , Parada Cardíaca/complicações , Parada Cardíaca/epidemiologia , Parada Cardíaca/terapia , Humanos , Incidência , Alta do Paciente , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Sobreviventes
8.
PLoS Genet ; 13(8): e1006974, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28827832

RESUMO

Mlh1-Mlh3 is an endonuclease hypothesized to act in meiosis to resolve double Holliday junctions into crossovers. It also plays a minor role in eukaryotic DNA mismatch repair (MMR). To understand how Mlh1-Mlh3 functions in both meiosis and MMR, we analyzed in baker's yeast 60 new mlh3 alleles. Five alleles specifically disrupted MMR, whereas one (mlh3-32) specifically disrupted meiotic crossing over. Mlh1-mlh3 representatives for each class were purified and characterized. Both Mlh1-mlh3-32 (MMR+, crossover-) and Mlh1-mlh3-45 (MMR-, crossover+) displayed wild-type endonuclease activities in vitro. Msh2-Msh3, an MSH complex that acts with Mlh1-Mlh3 in MMR, stimulated the endonuclease activity of Mlh1-mlh3-32 but not Mlh1-mlh3-45, suggesting that Mlh1-mlh3-45 is defective in MSH interactions. Whole genome recombination maps were constructed for wild-type and MMR+ crossover-, MMR- crossover+, endonuclease defective and null mlh3 mutants in an S288c/YJM789 hybrid background. Compared to wild-type, all of the mlh3 mutants showed increases in the number of noncrossover events, consistent with recombination intermediates being resolved through alternative recombination pathways. Our observations provide a structure-function map for Mlh3 that reveals the importance of protein-protein interactions in regulating Mlh1-Mlh3's enzymatic activity. They also illustrate how defective meiotic components can alter the fate of meiotic recombination intermediates, providing new insights for how meiotic recombination pathways are regulated.


Assuntos
Recombinação Homóloga/genética , Proteína 1 Homóloga a MutL/genética , Proteínas MutL/genética , Mapas de Interação de Proteínas/genética , Proteínas de Saccharomyces cerevisiae/genética , Alelos , Troca Genética , Reparo de Erro de Pareamento de DNA/genética , Genoma Fúngico , Meiose/genética , Saccharomyces cerevisiae/genética , Relação Estrutura-Atividade
9.
J Electrocardiol ; 63: 153-158, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31668456

RESUMO

BACKGROUND: The overall risk of atrial fibrillation (AF) among patients with pacemaker (PM) in comparison to control cohort is unknown. PURPOSE: To investigate the risk of AF after implantation of a PM in an AF-naive population in comparison to an age- and sex-matched PM- and AF-free population cohort. METHODS: All patients with a dual chamber PM (DDD) implanted between 2000 and 2014 without a known history of AF were included (n = 17,428). To compare, a general population cohort without pacemaker and a cohort with loop recorder was identified. Outcome was the cumulative incidence of AF within the first 2 years from 3-months after device implantation. RESULTS: At the end of first 3-months after device implantation, 16,383 patients were free of AF and were included in the current study. In comparison to controls (n = 86,167), patients with PM had higher cumulative incidence of AF (5.2% vs 2.7%, P < 0.001)). Due to interaction with age, patients were divided into three age-groups) and the relative risk for the diagnosis of AF were: < 70 years (HR 4.46, 95% CI 3.65-5.44); 70-79 years (HR 2.60, 95% CI 2.27-2.98); and ≥ 80 years (HR 1.29, 95% CI 1.15-1.45). For comparison between PM and loop-recorder cohort (1:1 matching), 2202 patients were available in both groups. The incidence of AF within the first 2-years in the both groups was 7.9% vs. 8.4% (loop vs pacemaker). CONCLUSIONS: Patients with PM have an increased risk of being diagnosed with AF in comparison to general cohort likely due to continuous monitoring.


Assuntos
Fibrilação Atrial , Marca-Passo Artificial , Idoso , Fibrilação Atrial/epidemiologia , Dinamarca/epidemiologia , Eletrocardiografia , Seguimentos , Humanos , Sistema de Registros
10.
J Environ Manage ; 259: 109782, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32072951

RESUMO

The steel industry is the largest consumer of energy in the world among industrial sectors. It is generally acknowledged that energy and environment are intimately related. Steel production is an energy intensive process that has a significant environmental impact. This paper reviews the progress made on energy consumption, carbon dioxide emissions and water consumption in the steel industry worldwide. The reduction in the availability of fresh water resources combined with the effects of global warming and climate change have increased pressure on industries, especially steel, to reduce its overall pollution, and specifically its water and carbon footprint. The implications of these effects on the value chain is discussed in this review. The contribution of new emerging technologies of iron and steelmaking is also reviewed. Finally, the important issues that contribute to define a sustainable industrial activity such as the recycling of steel and of by-products of steel production are studied. The history of steel industry is full of lessons, one of which is the need to keep the dreams alive. There are indeed expectations to solve problems created by technical progress.


Assuntos
Indústrias , Aço , Pegada de Carbono , Poluição Ambiental , Recursos Hídricos
11.
Cell Immunol ; 338: 27-31, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30928016

RESUMO

BACKGROUND: Recently various types of immunotherapies have made immense progress in combating cancer. Adoptive cell therapy, being one of the most favorable forms of immunotherapy, is rapidly moving from bench to bed. MAIN BODY: Different types of T-memory cells are being used as promising candidates for adoptive cell therapy: T effector memory (TEM) cells which are terminally differentiated memory cells and attain effector function soon after re-stimulation; T central memory (TCM) cells which differentiate into effector T-memory subsets and T-effector cells after antigenic stimulation; and tissue T resident memory (TRM) cells which fight the tumor insult at the peripheral tissues. Recently, a new subtype of T-memory cells, T stem cell memory (TSCM) have been identified as the most favorable candidate for adoptive cell therapy as they exhibit higher persistence, anti-tumor immunity and self-renewal capacity in the tumor-bearing host. CONCLUSION: In this review, we briefly describe the concept and types of T-memory cells as well as their role as potential candidates for anti-cancer immunotherapy.


Assuntos
Imunoterapia Adotiva/métodos , Neoplasias/terapia , Linfócitos T/imunologia , Animais , Diferenciação Celular , Autorrenovação Celular , Citotoxicidade Imunológica , Humanos , Memória Imunológica , Neoplasias/imunologia , Células-Tronco
12.
IUBMB Life ; 70(8): 743-752, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29934971

RESUMO

Diploid organisms undergo meiosis to produce haploid germ cells. Crossover events during meiosis promote genetic diversity and facilitate accurate chromosome segregation. The baker's yeast Saccharomyces cerevisiae is extensively used as a model for analysis of meiotic recombination. Conventional methods for measuring recombination events in S. cerevisiae have been limited by the number and density of genetic markers. Next generation sequencing (NGS)-based analysis of hybrid yeast genomes bearing thousands of heterozygous single nucleotide polymorphism (SNP) markers has revolutionized analysis of meiotic recombination. By facilitating analysis of marker segregation in the whole genome with unprecedented resolution, this method has resulted in the generation of high-resolution recombination maps in wild-type and meiotic mutants. These studies have provided novel insights into the mechanism of meiotic recombination. In this review, we discuss the methodology, challenges, insights and future prospects of using NGS-based methods for whole genome analysis of meiotic recombination. The objective is to facilitate the use of these high through-put sequencing methods for the analysis of meiotic recombination given their power to provide significant new insights into the process. © 2018 The Authors. IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 70(8):743-752, 2018.


Assuntos
Genoma Fúngico/genética , Meiose/genética , Recombinação Genética , Saccharomyces cerevisiae/genética , Segregação de Cromossomos/genética , Sequenciamento de Nucleotídeos em Larga Escala , Polimorfismo de Nucleotídeo Único/genética
13.
J Environ Manage ; 218: 234-244, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-29680755

RESUMO

A cyanobacterial strain, Synechococcus sp. NIT18, has been applied to sequester CO2 using sodium carbonate as inorganic carbon source due to its efficiency of CO2 bioconversion and high biomass production. The biomass obtained is used for the extraction of biomolecules - protein, carbohydrate and lipid. The main objective of the study is to maximize the biomass and biomolecules production with CO2 sequestration using cyanobacterial strain cultivated under different concentrations of CO2 (5-20%), pH (7-11) and inoculum size (5-12.5%) within a statistical framework. Maximum sequestration of CO2 and maximum productivities of protein, carbohydrate and lipid are 71.02%, 4.9 mg/L/day, 6.7 mg/L/day and 1.6 mg/L/day respectively, at initial CO2 concentration: 10%, pH: 9 and inoculum size: 12.5%. Since flue gas contains 10-15% CO2 and the present strain is able to sequester CO2 in this range, the strain could be considered as a useful tool for CO2 mitigation for greener world.


Assuntos
Dióxido de Carbono , Sequestro de Carbono , Biomassa , Carbono , Cianobactérias , Lipídeos
14.
Water Sci Technol ; 75(7-8): 1572-1583, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28402298

RESUMO

Methylene blue (MB) commonly found in the textile industry effluent has been chosen as a model dye to investigate bioremediation using Bacillus subtilis MTCC 441. Both free cells and calcium alginate immobilized cells have been used to remove MB from the effluent. The operating variables of initial concentration of dye (20-60 mg/L), inoculum size (4-8%) and temperature (25-35 °C) have been varied judiciously during the kinetic study in a batch contactor. A maximum removal of 91.68% is obtained when 20 mg/L MB solution was inoculated with 8% inoculum and cultured for 6 h at 30 °C. Continuous removal of MB has been studied in a fixed bed contactor using immobilized cells as packing materials. Influent concentration (10-30 mg/L) was varied and breakthrough parameters have been determined. With increase in influent concentration from 10 mg/L to 30 mg/L, percentage removal of dye decreases from 72.44% to 49.62%.


Assuntos
Bacillus subtilis/metabolismo , Corantes/metabolismo , Azul de Metileno/metabolismo , Poluentes Químicos da Água/metabolismo , Adsorção , Biodegradação Ambiental , Concentração de Íons de Hidrogênio , Cinética , Temperatura , Indústria Têxtil
15.
Asian-Australas J Anim Sci ; 29(11): 1523-1529, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26954129

RESUMO

Soybean meal (SBM), a commonly used protein source for animal feed, contains anti-nutritional factors such as trypsin inhibitor, phytate, oligosaccharides among others, which limit its utilization. Microbial fermentation using bacteria or fungi has the capability to improve nutritional value of SBM by altering the native composition. Both submerged and solid state fermentation processes can be used for this purpose. Bacterial and fungal fermentations result in degradation of various anti-nutritional factors, an increase in amount of small-sized peptides and improved content of both essential and non-essential amino acids. However, the resulting fermented products vary in levels of nutritional components as the two species used for fermentation differ in their metabolic activities. Compared to SBM, feeding non-ruminants with fermented SBM has several beneficial effects including increased average daily gain, improved growth performance, better protein digestibility, decreased immunological reactivity and undesirable morphological changes like absence of granulated pinocytotic vacuoles.

16.
Artigo em Inglês | MEDLINE | ID: mdl-38498762

RESUMO

Dynamic disease pathways are a combination of complex dynamical processes among bio-molecules in a cell that leads to diseases. Network modeling of disease pathways considers disease-related bio-molecules (e.g. DNA, RNA, transcription factors, enzymes, proteins, and metabolites) and their interaction (e.g. DNA methylation, histone modification, alternative splicing, and protein modification) to study disease progression and predict therapeutic responses. These bio-molecules and their interactions are the basic elements in the study of the misregulation in the disease-related gene expression that lead to abnormal cellular responses. Gene regulatory networks, cell signaling networks, and metabolic networks are the three major types of intracellular networks for the study of the cellular responses elicited from extracellular signals. The disease-related cellular responses can be prevented or regulated by designing control strategies to manipulate these extracellular or other intracellular signals. The paper reviews the regulatory mechanisms, the dynamic models, and the control strategies for each intracellular network. The applications, limitations and the prospective for modeling and control are also discussed.

17.
Chem Asian J ; : e202400419, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38872363

RESUMO

Supramolecular gels are an important class of materials that are promising for its wide range of applications including drug delivery. While supramolecular gels are intrinsically porous because of the 3D nano-matrix (gel matrix) that is being formed due to supramolecular self-assembly process involving the gelator molecules during gelation, additional nanopores can be introduced to the overall gel if the gelator molecule itself holds molecular cavity such as metal-organic-cage (MOC) molecules. A MOC having the molecular formula [(Pd2L24).4NO3].3H2O.2DMF.MeOH (Pd-cage) (L2=5-Azido-N,N'-di-pyridin-3-yl-isophthalamide) was successfully synthesized and characterized by FT-IR, 1H NMR, ESI-MS and single crystal X-ray diffraction. Stimuli-reversible supramolecular metallogel PdG could easily be formed from Pd-cage in DMSO/water mixture. The molecular cage of Pd-cage was demonstrated to be available for loading an anti-cancer drug namely doxorubicin (DOX). Subsequently, DOX was also loaded within PdG and delivered to melanoma cell line B16-F10 displaying significant anti-cancer activity as revealed by both MTT and scratch assay. Rheoreversibility of PdG and its ability to load and deliver DOX to cancer cells clearly raised hope for developing this metallogel further as topical anticancer gel.

18.
J Cardiovasc Dev Dis ; 11(2)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38392278

RESUMO

Over the past two decades of CRT use, the failure rate has remained around 30-35%, despite several updates in the guidelines based on the understanding from multiple trials. This review article summarizes the role of mechanical dyssynchrony in the selection of heart failure patients for cardiac resynchronization therapy. Understanding the application of mechanical dyssynchrony has also evolved during these past two decades. There is no role of lone mechanical dyssynchrony in the patient selection for CRT. However, mechanical dyssynchrony can complement the electrocardiogram and clinical criteria and improve patient selection by reducing the failure rate. An oversimplified approach to mechanical dyssynchrony assessment, such as just estimating time-to-peak delays between segments, should not be used. Instead, methods that can identify the underlying pathophysiology of HF and are representative of a substrate to CRT should be applied.

19.
Front Bioeng Biotechnol ; 12: 1362681, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38903193

RESUMO

Chemotherapy drugs like doxorubicin (Dox) are widely used in middle-income countries around the world to treat various types of cancers, including breast cancer. Although they are toxic, they are still widely used to treat cancer. Delivering chemotherapy drugs directly to cancer cells to reduce side effects remains a challenge. Moreover, modern research gave rise to cancer stem cell theory, which implicated cancer stem cells in tumor initiation, progression, and relapse. This makes it imperative to target cancer stem cells to achieve complete remission. Our work highlights the development of an exosome-based targeted drug delivery vehicle. These exosomes were isolated from mature dendritic cells (mDCs) and encapsulated with doxorubicin (ExoDS). Our results showed that ExoDS specifically targeted breast cancer cells and breast cancer stem cells. Further analysis revealed that ExoDS did not induce any significant apoptosis in healthy mammary cells and peripheral blood mononuclear cells (PBMCs) isolated from healthy individuals and breast cancer patients. ExoDS was also found to target circulating tumor cells (CTCs) isolated from patient blood. ExoDS also showed equal efficiency compared to free doxorubicin in vivo. We also observed that ExoDS reduced the expression of cancer stem cell markers in murine tumor tissues. Altogether, this work provides novel insights into how mDC-derived exosomes can be used to specifically target cancer cells and cancer stem cells.

20.
Int J Cardiol ; 398: 131595, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37984715

RESUMO

BACKGROUND: The knowledge of prognosis following out-of-hospital cardiac arrest (OHCA) in patients with heart failure heart failure (HF) is sparse. The objective of this study was to compare the outcome after OHCA among patients with and without HF. METHODS: We studied 45,293 patients who were included for the Danish cardiac arrest registry between 2001 and 2014. Patients were stratified into two groups based on the presence of HF prior to cardiac arrest. The primary outcome was 30-day survival and secondary outcome was anoxic brain damage or permanent nursing home admission at 1-year among 30-day survivors. RESULTS: Among the final 28,955 patients included, 6675 (23%) patients had prior HF and 22,280 (77%) patients had no prior HF. At 30 days, 616 (9.2%) patients survived among the patients with HF and 1916 (8.6%) among the patients without HF. There was a significant interaction between atrial fibrillation (AF) and HF for primary outcome and therefore it was assessed separately between the two study groups stratified based on AF. Among patients without AF a significantly higher odds of 30-day survival were observed among patients with HF (OR 2.69, 95% CI 2.34-3.08, P < 0.001), but no difference was observed among the patients from two study groups with no AF. No significant difference in risk for secondary outcome was observed among the two study groups. In multivariable average treatment effect modeling, all the results largely remain unchanged. CONCLUSIONS: Outcome following OHCA among patients with and without HF is found to be similar in this large Danish OHCA registry.


Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Parada Cardíaca Extra-Hospitalar , Humanos , Parada Cardíaca Extra-Hospitalar/diagnóstico , Parada Cardíaca Extra-Hospitalar/epidemiologia , Parada Cardíaca Extra-Hospitalar/terapia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/complicações , Hospitalização , Sistema de Registros
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